U.S. patent number 8,701,657 [Application Number 12/541,141] was granted by the patent office on 2014-04-22 for systems for generating nitric oxide.
This patent grant is currently assigned to Geno LLC. The grantee listed for this patent is David H. Fine, Bryan Johnson, Gregory Vasquez. Invention is credited to David H. Fine, Bryan Johnson, Gregory Vasquez.
United States Patent |
8,701,657 |
Fine , et al. |
April 22, 2014 |
Systems for generating nitric oxide
Abstract
In one aspect, a system for delivering nitric oxide to a patient
can include a first gas source including nitrogen dioxide mixed in
air or oxygen, a second gas source supplying compressed air, a
ventilator coupled to the first and second gas sources, where the
ventilator can be resistant to nitrogen dioxide, and where the
ventilator provides a gas flow having a proper amount of nitrogen
dioxide, one or more conversion devices operably coupled to the
ventilator, where the conversion devices covert nitrogen dioxide
into nitric oxide, and a patient interface operably coupled to the
conversion devices, where the patient interface delivers nitric
oxide to the patient.
Inventors: |
Fine; David H. (Cocoa, FL),
Vasquez; Gregory (Cocoa, FL), Johnson; Bryan (Merritt
Island, FL) |
Applicant: |
Name |
City |
State |
Country |
Type |
Fine; David H.
Vasquez; Gregory
Johnson; Bryan |
Cocoa
Cocoa
Merritt Island |
FL
FL
FL |
US
US
US |
|
|
Assignee: |
Geno LLC (Cocoa, FL)
|
Family
ID: |
41695167 |
Appl.
No.: |
12/541,141 |
Filed: |
August 13, 2009 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20100043789 A1 |
Feb 25, 2010 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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61090616 |
Aug 21, 2008 |
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Current U.S.
Class: |
128/202.26;
128/203.12; 128/204.18 |
Current CPC
Class: |
A61M
16/12 (20130101); A61M 16/0051 (20130101); A61M
16/10 (20130101); C01B 21/24 (20130101); A61M
16/20 (20130101); A61M 2202/0275 (20130101); A61M
2016/102 (20130101); A61M 16/16 (20130101) |
Current International
Class: |
A61M
15/00 (20060101); A61M 16/00 (20060101); A62B
7/08 (20060101); A62B 21/00 (20060101) |
Field of
Search: |
;128/202.26,203.12,203.22,204.14,204.18,205.25 ;95/128,129
;422/120,122,129,177 ;423/402 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Miller, Celermajer, Deanfield, Macrae. Guidelines for the safe
administration of inhaled nitric oxide. 1994. Archives of Disease
in Childhood. vol. 70. pp. F47-F49. cited by examiner.
|
Primary Examiner: Young; Rachel
Attorney, Agent or Firm: Steptoe & Johnson LLP
Parent Case Text
CLAIM OF PRIORITY
This application claims the benefit of prior U.S. Provisional
Application No. 61/090,616, filed on Aug. 21, 2008, which is
incorporated by reference in its entirety.
Claims
What is claimed:
1. A system for delivering nitric oxide to a patient, comprising: a
first gas source including nitrogen dioxide premixed in air or
oxygen; a second gas source supplying compressed air; a ventilator
coupled to the first and second gas sources; a mixing valve which
is connected to both the first gas source and the second gas source
downstream of both the first gas source and the second gas source,
wherein the mixing valve is resistant to NO.sub.2 gases; one or
more conversion devices operably coupled to the ventilator, wherein
the one or more conversion devices include an inlet, a chamber
containing a matrix, wherein the matrix is positioned within the
chamber and a space between the chamber and the matrix, and a
diverter positioned between the inlet and the chamber, wherein the
diverter is configured to direct a gas flow to the space between
the chamber and the matrix, and wherein the one or more conversion
devices convert nitrogen dioxide into nitric oxide; and a patient
interface operably coupled to the one or more conversion devices,
wherein the patient interface delivers nitric oxide to the
patient.
2. The system of claim 1, further comprising a third gas source
supplying compressed oxygen, wherein the third gas source is in
communication with the ventilator.
3. The system of claim 1, further comprising a humidifier
positioned between the ventilator and the one or more conversion
devices.
4. The system of claim 1, comprising a first conversion device of
the one or more conversion devices, wherein a humidifier is
integral with the first conversion device.
5. The system of claim 1, comprising a first conversion device of
the one or more conversion devices and a second conversion device
of the one or more conversion devices, wherein a humidifier is
integral with the second conversion device.
6. The system of claim 1, comprising a first conversion device of
the one or more conversion devices, a second conversion device of
the one or more conversion devices and a humidifier, wherein the
humidifier is positioned between the first conversion device and
the patient interface and before the second conversion device.
7. The system of claim 1, wherein the mixing valve is within the
ventilator.
Description
TECHNICAL FIELD
This description relates to systems for generating nitric
oxide.
BACKGROUND
Nitric oxide (NO), also known as nitrosyl radical, is a free
radical that is an important signaling molecule. For example, NO
causes smooth muscles in blood vessels to relax, thereby resulting
in vasodilation and increased blood flow through the blood vessel.
These effects are limited to small biological regions since NO is
highly reactive with a lifetime of a few seconds and is quickly
metabolized in the body.
Typically, NO gas is supplied in a bottled gaseous form diluted in
nitrogen gas (N.sub.2). Great care has to be taken to prevent the
presence of even trace amounts of oxygen (O.sub.2) in the tank of
NO gas because NO, in the presence of O.sub.2, is oxidized into
nitrogen dioxide (NO.sub.2). Unlike NO, the part per million levels
of NO.sub.2 gas is highly toxic if inhaled and can form nitric and
nitrous acid in the lungs.
SUMMARY
Briefly, and in general terms, various systems generating nitric
oxide are disclosed herein. According to one embodiment, the system
includes a first gas source providing nitrogen dioxide mixed in air
or oxygen, and a second gas source supplying compressed air and/or
compressed oxygen. The system also includes a ventilator coupled to
the first and second gas sources, wherein the ventilator is
resistant to nitrogen dioxide. The ventilator regulates gas flow
and allows for the adjustment of nitrogen dioxide concentration in
the gas flow. The system further includes one or more conversion
devices operably coupled to the ventilator where the conversion
devices convert nitrogen dioxide into nitric oxide. A patient
interface delivers nitric oxide to the patient and is operably
coupled to the conversion devices.
In another embodiment, the system includes a humidifier that is
placed prior to the first conversion device. In yet another
embodiment, the humidifier is integral with the conversion device.
Optionally, the system includes an active humidifier that is placed
prior to a second conversion cartridge which is adjacent to the
patient interface.
The system allows oxygen and nitric oxide levels to be varied
independently. The system also includes safeguards in the event of
system failure. In one embodiment, the main conversion cartridge in
the system is designed to have sufficient capacity to convert the
entire contents of more than one bottle of nitrogen dioxide in the
event of system failure. In another embodiment, a second conversion
cartridge is also included as a redundant safety measure where the
second conversion cartridge is able to convert the entire contents
of a bottle of nitrogen dioxide into nitric oxide.
Other features will become apparent from the following detailed
description, taken in conjunction with the accompanying drawings,
which illustrate by way of example, the features of the various
embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic view of one embodiment of a nitric oxide (NO)
generating system.
FIG. 2 is a block diagram of one embodiment of a NO generating
system.
FIG. 3 is a perspective view of one embodiment of a system for
delivering NO to a patient.
FIG. 4 is a cross-sectional view of one embodiment of a NO
generating device.
FIG. 5 is a block diagram of another embodiment of a NO generating
device.
DETAILED DESCRIPTION
Various systems and devices for generating nitric oxide (NO) are
disclosed herein. Generally, NO is inhaled or otherwise delivered
to a patient's lungs. Since NO is inhaled, much higher local doses
can be achieved without concomitant vasodilation of the other blood
vessels in the body. Accordingly, NO gas having a concentration of
approximately 2 to approximately 1000 ppm (e.g., greater than 2,
20, 40, 80, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600,
650, 700, 750, 800, 850, 900, 950, 1000, 1200, 1400, 1600, 1800 and
2000 ppm) may be delivered to a patient. Accordingly, high doses of
NO may be used to prevent, reverse, or limit the progression of
disorders which can include, but are not limited to, acute
pulmonary vasoconstriction, traumatic injury, aspiration or
inhalation injury, fat embolism in the lung, acidosis, inflammation
of the lung, adult respiratory distress syndrome, acute pulmonary
edema, acute mountain sickness, post cardiac surgery acute
pulmonary hypertension, persistent pulmonary hypertension of a
newborn, perinatal aspiration syndrome, haline membrane disease,
acute pulmonary thromboembolism, heparin-protamine reactions,
sepsis, asthma, status asthmaticus, or hypoxia. NO can also be used
to treat chronic pulmonary hypertension, bronchopulmonary
dysplasia, chronic pulmonary thromboembolism, idiopathic pulmonary
hypertension, primary pulmonary hypertension, or chronic
hypoxia.
Currently, approved devices and methods for delivering inhaled NO
gas require complex and heavy equipment, and they are limited in
their output to 80 ppm of NO because of the presence of the toxic
compound, nitrogen dioxide (NO.sub.2). NO gas is stored in heavy
gas bottles with nitrogen and no traces of oxygen. NO gas is mixed
with air or oxygen with specialized injectors and complex
ventilators, and the mixing process is monitored with equipment
having sensitive microprocessors and electronics. All this
equipment is required in order to ensure that NO is not oxidized
into NO.sub.2 during the mixing process since NO.sub.2 is highly
toxic. However, this equipment is not conducive to use in routine
hospital and non-medical facility settings since the size, cost,
complexity, and safety issues restrict the operation of this
equipment to highly-trained professionals who are specially trained
in its use.
FIGS. 1-2 illustrate one embodiment of a system 100 that generates
NO from NO.sub.2. The system 100 may be used in a medical setting
such as, but not limited to, an operating theatre or an intensive
care unit. The system 100 includes a gas source 102 containing
NO.sub.2 premixed in air 106 or oxygen 108. As shown in FIG. 1, the
system 100 includes two gas sources 102 where one bottle is a
standby in the event the first bottle becomes depleted.
Alternatively, the system 100 may include a single gas source
capable of producing NO. In another embodiment, the system 100 may
include a plurality of gas sources capable of producing NO.
Optionally, if more than one gas source is provided with the system
100, a valve (not shown) is coupled to the gas sources and allows
for switching between the gas sources.
The system 100 includes a ventilator 104 connected to the gas
sources 102 capable of producing NO in addition to a gas source of
compressed air 106 and oxygen 108, as shown in FIG. 1. The
ventilator 104 also includes components such as mixing valves 117,
118 that are resistant to NO.sub.2 gas. In one embodiment, the
mixing valves 117, 118 used in the ventilator 102 are manufactured
by Bio-Med Devices of Guilford, Conn. The ventilator 104 is also
provided with controls to independently vary the concentration of
NO.sub.2 and oxygen 108. Accordingly, the mixing valves 117, 118
and the ventilator 104 regulate and adjust the concentration of the
gas so that it is at a proper concentration to be converted into a
therapeutic dose of NO at the main conversion cartridge 110.
Additionally, the ventilator 104 can be adjusted to provide the
proper gas flow pattern.
As shown in FIGS. 1-2, the gas passes through the main conversion
cartridge 110 where NO.sub.2 in the gas flow is converted to NO. In
one embodiment, a passive humidifier (not shown) is positioned to
the main cartridge 110. The passive humidifier operates at a dew
point of approximately less than 18.degree. C. (not shown) that may
be separate or integral with the main cartridge 110. The NO gas
generated by the main conversion cartridge 110 then flows through
an active humidifier 114, which provides moisture to the patient
and also extends the lifespan of the conversion cartridge 112. The
humidified NO gas then filters through a secondary cartridge 112
(also referred to as a recuperator) to convert any NO.sub.2 in the
gas lines into NO. The NO gas (in air or oxygen) is then delivered
to a patient via a patient interface 116. The patient interface 116
may be a mouth piece, nasal cannula, face mask, or fully-sealed
face mask. The active humidifier brings the moisture content of the
NO gas (and air/oxygen) up to a dew point of approximately 32 to
37.degree. C., thereby preventing moisture loss from the lungs.
As shown in FIGS. 1-2, a single humidifier 114 is positioned
between the conversion cartridges 110, 112. In another embodiment,
the system 100 may include humidifiers 114 placed prior to each
conversion cartridge 110, 112. As shown in FIGS. 1-2, the
humidifier 114 is a separate device, but it is contemplated that
the humidifier may be an integral component of each conversion
cartridge (not shown). According to one embodiment, the humidifier
114 used in the system 100 is manufactured by Fisher and
Pykell.
Additionally, the system 100 may include one or more safety
features. In one embodiment, the main conversion cartridge 110 is
sized so that it has excess capacity to convert NO.sub.2 into NO.
For example, the main conversion cartridge 110 is sized to convert
the entire contents of more than one gas source 102 of NO.sub.2
gas. If the main conversion cartridge 110 were to fail, the
recuperator cartridge 112 has sufficient capacity to convert the
entire contents of a gas bottle 102. In yet another embodiment,
NO.sub.2 and the NO gas concentrations may be monitored after the
main conversion cartridge 110. In one embodiment, the gas
concentrations of NO and NO.sub.2 may be monitored by one or more
NO and NO.sub.2 detectors manufactured by Cardinal Healthcare,
Viasys Division. If any NO.sub.2 is detected, visual and/or
auditory alarms would be presented to the operator. The alarms will
allow the operator to correct the problem, but the recuperator
cartridge 112 would convert any NO.sub.2 that was present in the
gas lines back into NO. This function is important at very high NO
levels (>40 ppm) as well as during start up of the system 100.
Additionally, the recuperator cartridge 112 makes it unnecessary to
flush the lines to remove NO.sub.2, since the NO.sub.2 in the lines
would be converted to NO by the recuperator prior to delivery to a
patient.
FIG. 3 illustrates another embodiment of a system 300 for
delivering NO to a patient. The system 300 is provided on a wheeled
stand 302. The system 300 includes a ventilator 104 that is
resistant to NO.sub.2 gas. The system 300 also includes two gas
sources 102 for providing NO.sub.2 gas. Additionally, a third gas
source 306 is also mounted in the center of the stand 302. The
third gas source 306 contains NO.sub.2 in air or oxygen at an
appropriate concentration. The third gas source 306 is also
connected to the ventilator 104 by gas plumbing 304 and is in a
standby mode. In the event of a disruption of the NO.sub.2 gas,
compressed air, or compressed oxygen, an automatic series of valves
would shut down the feed of gas to the ventilator 104 and replace
it with gas from the back up gas source 306. This safety feature is
on standby mode and may be implemented within the time frame of a
single breath. If the ventilator 104 malfunctions, the third gas
source 306 is available as substitute for the system 300. The third
gas source 306 includes a NO conversion cartridge 308 and may be
used to deliver NO to the patient by means of a handheld ventilator
(not shown).
Conversion Cartridges
FIG. 4 illustrates one embodiment of a device 400 that generates NO
from NO.sub.2. The device 100, which may be referred to as a NO
generation cartridge, a GENO cartridge, a GENO cylinder, or a
recuperator, includes a body 402 having an inlet 404 and an outlet
406. The inlet 404 and outlet 406 are sized to engage gas plumbing
lines or directly couple to other components such as, but not
limited to, gas tanks, regulators, valves, humidifiers, patient
interfaces, or recuperators. Additionally, the inlet 404 and outlet
406 may include threads or specially designed fittings to engage
these components.
As shown in FIG. 4, the body 402 is generally cylindrical in shape
and defines a cavity that holds a porous solid matrix 408.
According to one embodiment, the porous solid matrix 408 is a
mixture of a surface-activated material such as, but not limited
to, silica gel and one or more suitable thermoplastic resins. The
thermoplastic resin, when cured, provides a rigid structure to
support the surface-activated material. Additionally, the porous
thermoplastic resin may be shaped or molded into any form.
According to one embodiment, the porous solid matrix 408 is
composed of at least 20% silica gel. In another embodiment, the
porous solid matrix 408 includes approximately 20% to approximately
60% silica gel. In yet another embodiment, the porous solid matrix
408 is composed of 50% silica gel. As those skilled in the art will
appreciate, any ratio of silica gel to thermoplastic resin is
contemplated so long as the mechanical and structural strength of
the porous solid matrix 408 is maintained. In one embodiment, the
densities of the silica gel and the thermoplastic resin are
generally similar in order to achieve a uniform mixture and,
ultimately, a uniform porous solid matrix 408.
As shown in FIG. 4, the porous solid matrix 408 also has a
cylindrical shape having an inner bore 412. In other embodiments,
the porous solid matrix may have any shape known or developed in
the art. The porous solid matrix 408 is positioned within the body
402 such that a space 414 is formed between the body and the porous
solid matrix 408. At the inlet end 404 of the body 402, a diverter
410 is positioned between the inlet and the porous solid matrix
408. The diverter 410 directs the gas flow to the outer diameter of
the porous solid matrix 408 (as shown by the white arrows). Gas
flow is forced through the porous solid matrix 408 whereby any
NO.sub.2 is converted into NO (as shown by the darkened arrows). NO
gas then exits the outlet 406 of the device 400. The porous solid
matrix 408 allows the device 400 to be used in any orientation
(e.g., horizontally, vertically, or at any angle). Additionally,
the porous solid matrix 408 provides a rigid structure suitable to
withstand vibrations and abuse associated with shipping and
handling.
FIG. 5 illustrates another embodiment of a conversion cartridge 500
that generates NO from NO.sub.2. The conversion cartridge 500
includes an inlet 505 and an outlet 510. Porous filters or a screen
and glass wool 515 are located at both the inlet 505 and the outlet
510, and the remainder of the cartridge 500 is filled with a
surface-active material 520 that is soaked with a saturated
solution of antioxidant in water to coat the surface-active
material. In the example of FIG. 5, the antioxidant is ascorbic
acid.
In a general process for converting NO.sub.2 to NO, an air flow
having NO.sub.2 is received through the inlet 505 and the air flow
is fluidly communicated to the outlet 110 through the
surface-active material 520 coated with the aqueous antioxidant. As
long as the surface-active material remains moist and the
antioxidant has not been used up in the conversion, the general
process is effective at converting NO.sub.2 to NO at ambient
temperatures.
The inlet 505 may receive the air flow having NO.sub.2, for
example, from a pressurized bottle of NO.sub.2, which also may be
referred to as a tank of NO.sub.2. The inlet 505 also may receive
an air flow with NO.sub.2 in nitrogen (N.sub.2), air, or oxygen
(O.sub.2). The inlet 505 may also receive the air flow having
NO.sub.2 from an air pump that fluidly communicates an air flow
over a permeation or a diffusion tube (not shown). The conversion
occurs over a wide concentration range. Experiments have been
carried out at concentrations in air of from about 0.2 ppm NO.sub.2
to about 100 ppm NO.sub.2, and even to over 1000 ppm NO.sub.2. In
one example, a cartridge that was approximately 5 inches long and
had a diameter of 0.8-inches was packed with silica gel that had
first been soaked in a saturated aqueous solution of ascorbic acid.
Other sizes of the cartridge are also possible. The moist silica
gel was prepared using ascorbic acid (i.e., vitamin C) designated
as A.C.S. reagent grade 99.1% pure from Aldrich Chemical Company
and silica gel from Fischer Scientific International, Inc.,
designated as S8 32-1, 40 of Grade of 35 to 70 sized mesh. Other
sizes of silica gel also are effective as long as the particles are
small enough and the pore size is such as to provide sufficient
surface area.
The silica gel was moistened with a saturated solution of ascorbic
acid that had been prepared by mixing 35% by weight ascorbic acid
in water, stirring, and straining the water/ascorbic acid mixture
through the silica gel, followed by draining. In one embodiment,
the silica gel is dried to about 30% moisture by weight. It has
been found that the conversion of NO.sub.2 to NO proceeds well when
the silica gel coated with ascorbic acid is moist. The conversion
of NO.sub.2 to NO does not proceed well in an aqueous solution of
ascorbic acid alone.
The cartridge filled with the moist silica gel/ascorbic acid was
able to convert 1000 ppm of NO.sub.2 in air to NO at a flow rate of
150 ml per minute, quantitatively, non-stop for over 12 days. A
wide variety of flow rates and NO.sub.2 concentrations have been
successfully tested, ranging from only a few ml per minute to flow
rates of up to approximately 5,000 ml per minute, up to flow rates
of approximately 80,000 ml per minute. The reaction also proceeds
using other common antioxidants, such as variants of vitamin E
(e.g., alpha tocopherol and gamma tocopherol).
The various embodiments described above are provided by way of
illustration only and should not be construed to limit the claimed
invention. Those skilled in the art will readily recognize various
modifications and changes that may be made to the claimed invention
without following the example embodiments and applications
illustrated and described herein, and without departing from the
true spirit and scope of the claimed invention, which is set forth
in the following claims.
* * * * *